Interpretive Summary: Chronic Granulomatous Disease (CGD) patients are at high risk for invasive aspergillosis (IA). The most common cause of IA in CGD patients is Aspergillus fumigatus followed by A. nidulans and rarely by other aspergilli. An undescribed Aspergillus species caused fatal IA refractory to therapy in CGD patients. We describe the new species and the symptoms that it causes. Recognizing the clinical manifestations, morphologic and genetic characteristics of the fungus will permit proper diagnosis and more informed patient management. This research will be of value to medical clinicians and mycologists.

Technical Abstract:
Two fatal IA cases and treatment regimens were reviewed. The fungus was characterized by mycological and molecular approaches. The combined sequence data of three loci, Mcm7, RPB2 and Tsr1, were used for phylogenetic analysis. Virulence of the new species was analyzed in corticosteroid treated BALB/C mice and CGD mice. Susceptibility of the species to triazoles and amphotericin B was compared with A. fumigatus using e-test. The new etiologic agent of IA was a species belonging to Aspergillus section Circumdati. The new species named Aspergillus tanneri was resistant to azoles and amphotericin B, and caused chronic disease which spread from the lung to adjacent organs. The infection caused by A. tanneri in CGD mice was considerably more chronic than by A. fumigatus. The two species, however, caused equally acute infection in corticosteroid treated mice. Unlike many species in the Circumdati section, ochratoxin was negative. This is the first report documenting IA in CGD patients due to a new Aspergillus species resistant to azoles and amphotericin B. Clinical manifestations were distinct from typical IA caused by A. fumigatus. The fungus is the first zoopathogenic species recognized in the Aspergillus section Circumdati. This study will assist future diagnosis of A. tanneri infection